What is the impact of antibiotic exposure on the risk of inflammatory bowel disease?

By Pooja Toshniwal PahariaJan 12 2023Reviewed by Danielle Ellis, B.Sc.

In a recent study published in Gut, researchers evaluated the impact of antibiotic usage on inflammatory bowel disease (IBD) development risk among individuals aged ten years and above.

Background

IBD refers to a chronic immunological condition affecting the bowel, comprising mainly two subtypes, i.e., Crohn’s disease (CD) and ulcerative colitis (UC). Studies have reported an increase in IBD cases due to suspected environmental risk factors. Antibiotic usage has been related to IBD development in children; however, the potential IBD risk among adults with antibiotic exposure is unclear.

About the study

In the present population-based national cohort study, researchers investigated the association between the use of antibiotics and IBD development among individuals aged ≥10. Years.

Demographic data were obtained from the national CRS (civil registration system) of Denmark on individuals aged ≥10 years, residing in Denmark for ≥5.0 years, and having no IBD history between January 1, 2000, and December 31, 2018. Data on prescribed medications were obtained from the Danish national prescription register in linkage with the civil registration system. Medications were coded based on the anatomical therapeutic chemical system.

Data obtained included medication codes and prescription dates, and the antibiotic medication fill/prescription date was considered the antibiotic use date. Antibiotic class dosage-response associations were evaluated based on the number of antibiotic courses, with antibiotics prescribed from the same class within a month of usage included under one antibiotic course.

Every antibiotic course contributed to an IBD risk period of one year to five years following exposure. In addition, sensitivity analysis was performed by extending the lag time from antibiotic exposure from one year to two years.

The national patient register of Denmark was utilized to obtain data on hospitalizations, outpatient and emergency department visits. IBD diagnosis was based on the ICD-8/10 (international classification of diseases eight or tenth revision) codes.

Antibiotic classes included penicillin with a narrow spectrum, penicillin with an extended spectrum, macrolides, nitrofurantoin, tetracyclines, and sulfonamides. In addition, fluoroquinolones and nitroimidazoles were included since the medications are frequently prescribed for treating gastrointestinal pathogen infections.

Data on socioeconomic status and urbanization (on the basis of the population/m²) were obtained by linking the residential address from the civil registration system with official statistics of Denmark. Medication history, particularly the use of PPI (proton pump inhibitors) and antifungal and antiviral medications, was recorded since the medications could alter the gut microbiota. Poisson regression analysis was performed, and the IRR (incidence rate ratios) values were determined.

Results

The study population comprised 6,104,245 individuals, followed up for 87,112,328 individual-years. Among the participants, 5,551,441 individuals (91%) had been prescribed ≥1.0 courses of antibiotics, and 52,898 new IBD cases (36,017 and 16,881 new UC and CD cases, respectively) were documented.

Antibiotic use increased IBD risks across ages, albeit the greatest risk was observed among individuals aged 40 years and above, with IRR values of 1.3, 1.5, and 1.5 for persons aged between 10 years and 40 years, between 40 years and 60 years, and 60 years and above, respectively. The finding was true for CD and UC, with a marginally greater risk for CD, with corresponding IRR values of 1.4, 1.6, and 1.5, respectively, compared to UC. 

Across ages, a positive dose-response association was observed, with comparable results for Crohn’s disease and ulcerative colitis. Similar findings were obtained in the sensitivity analysis. Each subsequent antibiotic course elevated IBD risk, with IRR values obtained with an increase in the antibiotic course of 1.1, 1.2, and 1.1 for persons aged between 10 and 40 years, between 40 and 60 years, and 60 years above, respectively. The greatest risk was observed for individuals prescribed ≥5.0 antibiotic courses across ages, with corresponding IRR values of 1.7, 2.1, and 2.0, respectively.

The greatest risk of IBD development was observed after one to two years of antibiotic use, and with every subsequent year, the risk was reduced. Particularly, for persons aged between 10 and 40 years, the IRR values were 1.4 one to two years post-antibiotic exposure and 1.1 four to five years post-exposure. Likewise, for persons aged between 40 years and 60 years, the IRR values were 1.7 one to two years post-antibiotic use and 1.2 four to five years post-use. For persons aged 60 years and above, the IRR values were 1.6 one to two years post-antibiotic use and 1.2 four to five years post-use, with similar results for Crohn’s disease and ulcerative colitis.

The greatest IBD risk was observed after using antibiotics that particularly target bacterial pathogens in the gastrointestinal tract. Only nitrofurantoin was not associated with IBD development across ages. The risk was greatest with nitroimidazoles, with IRR values of 1.3, 1.4, and 1.6 for persons aged between 10 and 40 years, between 40 and 60 years, and 60 years and above, respectively. The corresponding IRR values for fluoroquinolones were 1.8, 1.8, and 1.5, respectively. Similar results were obtained for Crohn’s disease and ulcerative colitis.

With advancing age, the gut microbial diversity reduces, increasing the susceptibility to disruptions, an effect potentiated by antibiotic exposure. Antibiotic usage can result in long-term intestinal microbial shifts that become increasingly prominent by repeated antibiotic courses, reducing microbial gut recovery.

Conclusion

Overall, the study findings showed that antibiotic usage increased the risk of IBD development, especially among individuals aged ≥40 years. The risk was greatest after ≥5.0 five antibiotic courses, within one to two years of antibiotic use, and exposure to antibiotics targeting gastrointestinal pathogenic organisms. The findings indicate that the gastrointestinal microbiota is a critical factor in IBD development, especially among older individuals.